In this study, we investigated whether selective activation of nociceptive primary afferent fibers by capsaicin would induce modulations on tooth-pulp-evoked sensory or inhibitory masseter reflex responses in healthy human subjects. The contribution of central N-methyl-D-aspartate (NMDA) receptor mechanisms in capsaicin-induced effects on sensory or reflex responses was evaluated by dextromethorphan, an NMDA-receptor antagonist. The inhibitory masseter reflex was evoked by electrical stimulation (constant current, single pulses) of the upper incisor while the subject was biting at 10% of his maximal force. The sensation of the tooth pulp stimulation was evaluated by visual analogue scale (VAS). The magnitude, duration, and the the latency of the reflex were determined by bite force measurements. The inhibitor masseter reflex could be induced by non-painful tooth pulp stimulation, and the inhibition was enhanced as a function of increasing stimulus intensity. Capsaicin (1%) applied topically to the skin of the cheek produced a spontaneous burning pain sensation. During capsaicin treatment, the VAS ratings for the sensation induced by tooth pulp stimulation were significantly reduced, whereas no significant changes were found in the tooth-pulp-induced masseter reflex responses. Double-blind treatment with dextromethorphan at a dose of 100 mg (= the highest does without side-effects) had no effect on sensory or reflex responses. These data indicate that noxious stimulation of the facial skin by capsaicin induces differential effects on tooth-pulp-evoked sensory and inhibitory masseter reflex responses: Sensory responses are strongly attenuated, while masseter reflex responses are not significantly changed. Dextromethorphan at a clinically applicable dose does not influence tooth-pulp-evoked sensory or reflex responses or their modulation by capsaicin. Furthermore, the lack of modulation of the masseter reflex response by capsaicin differs from the capsaicin-induced enhancement of a nocifensive limb flexion reflex described earlier.